The ryanodine receptor mediates early zymogen activation in pancreatitis
| Autor: | Wayne M. Grant, Fred S. Gorelick, Sohail Z. Husain, Thomas R. Kolodecik, Michael H. Nathanson, Priyajit Prasad |
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| Rok vydání: | 2005 |
| Předmět: |
Agonist
inorganic chemicals Male medicine.medical_specialty Trypsinogen medicine.drug_class Biology digestive system Models Biological Dantrolene Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Secretion Ceruletide Enzyme Precursors Multidisciplinary Microscopy Confocal Ryanodine receptor Secretory Vesicles Ryanodine Receptor Calcium Release Channel Biological Sciences musculoskeletal system Pancreas Exocrine Rats Endocrinology chemistry Pancreatitis Zymogen activation cardiovascular system Calcium tissues Intracellular medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(40) |
| ISSN: | 0027-8424 |
| Popis: | Acute pancreatitis is characterized by the pathologic activation of zymogens within pancreatic acinar cells. The process requires a rise in cytosolic Ca 2+ from undefined intracellular stores. We hypothesized that zymogen activation is mediated by ryanodine receptor (RYR)-regulated Ca 2+ release, because early zymogen activation takes place in a supranuclear compartment that overlaps in distribution with the RYR. Ca 2+ signals in the basolateral, but not apical, region of acinar cells observed during supraphysiologic agonist stimulation were dependent on RYR Ca 2+ release. Inhibition of RYR or depletion of RYR-sensitive Ca 2+ pools each reduced pathologic zymogen activation in isolated acinar cells, but neither treatment affected amylase secretion. Inhibition of RYR also inhibited zymogen activation in vivo . We propose that Ca 2+ release from the RYR mediates zymogen activation but not enzyme secretion. The findings imply a role for the RYR in acute pancreatitis. |
| Databáze: | OpenAIRE |
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